Contrasting effect of recombinant human erythropoietin on breast cancer cell response to cisplatin induced cytotoxicity

  • Nina Trošt Center for Functional Genomics and Bio-chips, Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Slovenia
  • Peter Juvan Center for Functional Genomics and Bio-chips, Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Slovenia
  • Gregor Serša Institute of Oncology, Department of Experimental Oncology, Ljubljana, Slovenia
  • Nataša Debeljak Center for Functional Genomics and Bio-chips, Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Slovenia and Medical Center for Molecular Biology, Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Slovenia

Abstract

Background. Human recombinant erythropoietin (rHuEpo) that is used for the treatment of the chemotherapy-induced anaemia in cancer patients was shown to cause detrimental effects on the course of disease due to increased adverse events inflicting patient’s survival, potentially related to rHuEpo-induced cancer progression. In this study, we elucidate the effect of rHuEpo administration on breast cancer cell proliferation and gene expression after cisplatin (cDDP) induced cytotoxicity

Materials and Methods. Two breast carcinoma models, MCF-7 and MDA-MB-231 cell lines, were used differing in oestrogen (ER) and progesterone (PR) receptors and  p53 status. Cells were cultured with or without rHuEpo for 24 h or 9 weeks and their growth characteristics after cDDP treatment were assessed together with expression of genes involved in the  p53-signaling pathway.

Results. Short-term exposure of breast cancer cells to rHuEpo lowers their proliferation and reduces cDDP cytotoxic potency. In contrast, long-term exposure of MCF-7 cells to rHuEpo increases proliferation and predisposes MCF-7 cells to cDDP cytotoxicity, but has no effect on MDA-MB-231 cells. MDA-MB-231 cells show altered level of ERK phosphorylation, indicating involvement of MAPK signalling pathway. Gene expression analysis of p53-dependent genes and bcl-2 gene family members confirmed differences between long and short-term rHuEpo effects, indicating the most prominent changes in BCL2 and BAD expression.

Conclusions. Proliferation and survival characteristics of MCF-7 cells are reversely modulated by the length of the rHuEpo exposure. On the other hand, MDA-MB-231 cells are almost irresponsive to long-term rHuEpo, supposedly due to the mutated p53 and ER(+)/PR(-) status. The p53 and ER/PR status may predict tumour response on rHuEpo and cDDP treatment.

Keywords: Breast cancer; erythropoietin; cisplatin; cytotoxicity

 

 

 

 

 

 

 

Published
2012-10-30
How to Cite
Trošt, N., Juvan, P., Serša, G., & Debeljak, N. (2012). Contrasting effect of recombinant human erythropoietin on breast cancer cell response to cisplatin induced cytotoxicity. Radiology and Oncology, 46(3). Retrieved from https://radioloncol.com/index.php/ro/article/view/741
Section
Experimental oncology